Fluorescence Detection of Prostate Cancer by an Activatable Fluorescence Probe for PSMA Carboxypeptidase Activity

Abstract

Prostate cancer (PCa) is a common malignant tumor among adult males, and convenient intraoperative detection of PCa would reduce the risk of leaving positive surgical margins, especially during nerve-sparing procedures. To achieve rapid, fluorescence-based visualization of PCa, we focused on the glutamate carboxypeptidase (CP) activity of prostate-specific membrane antigen (PSMA), a type II transmembrane glycoprotein that is attracting attention as a PCa biomarker. Based on our finding that aryl glutamate conjugates with an azoformyl linker are recognized by PSMA and have a sufficiently low LUMO (lowest unoccupied molecular orbital) energy level to quench the fluorophore through photoinduced electron transfer, we designed and synthesized a first-in-class activatable fluorescence probe for CP activity of PSMA. The developed probe allowed us to visualize the CP activity of PSMA in living cells and in clinical specimens from PCa patients and is expected to be useful for rapid intraoperative detection and diagnosis of PCa.

A molecular approach to rationally constructing specific fluorogenic substrates for the detection of acetylcholinesterase activity in live cells, mice brains and tissues

“…[9][10][11][12] Currently, several analytical methods based on colorimetric assays, 10,11 chemiluminescence, 12 electrochemical sensors, 13,14 nanoparticles, 15 and supramolecular assemblies, 16 have been engineered to probe AChE activity. Fluorescent probes combined with uorescence confocal imaging with unique features, [17][18][19][20][21][22][23][24][25][26][27][28] such as in situ and/or real-time detection, high spatiotemporal resolution and noninvasive monitoring abilities, have been extensively used in various disease diagnoses and therapies. 29,30 Currently, uorescent probes for AChE activity analysis employ acetyl groups as recognition units.…”

Activity‐Based Sensing: A Synthetic Methods Approach for Selective Molecular Imaging and Beyond

“…We will focus on ABS probes for diffusible small‐molecule and metal analytes, noting that such approaches for interrogating enzyme and nucleic acid activity can be applied to expand the ABS repertoire . Recent examples include work from Dickinson and co‐workers to monitor the depalmitoylation activity of acylprotein thioesterases, a study by Sessler, Shabat, Kim, and co‐workers to accelerate cleavage of a biomimetic electron reservoir for detection of NADPH: quinone oxidoreductase, and a report by the Urano and Kamiya groups on prostate‐specific membrane antigen (PSMA) carboxypeptidase …”

Aktivitätsbasierte Sensorik: ein synthetisch‐methodischer Ansatz für die selektive molekulare Bildgebung und darüber hinaus.

“…[73] Zu den aktuelleren Beispielen gehçren die Arbeiten von Dickinson et al zur Messung der Depalmitoylierungsaktivitätv on Acylprotein-Thioesterasen, [74] eine Studie von Sessler,S habat, Kim und Mitarbeitern zum beschleunigten Abbbau eines biomimetischen Elektronenreservoirs zum Nachweis der NADPH:Chinon-Oxidoreduktase [75] und eine Verçffentlichung aus den Labors von Urano und Kamiya über die prostataspezifische Membranantigen-(PSMA-)-Carboxypeptidase. [76] 4. Reaktionsklassen fürd ie aktivitätsbasierte Sensorik…”